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1.
J Cell Mol Med ; 28(15): e18537, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39120548

ABSTRACT

The association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease-related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein-protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.


Subject(s)
Colorectal Neoplasms , Computational Biology , Mendelian Randomization Analysis , Rectal Fistula , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Computational Biology/methods , Prognosis , Rectal Fistula/genetics , Protein Interaction Maps/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Gene Regulatory Networks , Genetic Predisposition to Disease , Gene Expression Profiling
2.
Discov Oncol ; 15(1): 357, 2024 Aug 18.
Article in English | MEDLINE | ID: mdl-39154317

ABSTRACT

BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

3.
BMC Biol ; 22(1): 169, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39135045

ABSTRACT

BACKGROUND: Numerous insect species undertake long-distance migrations on an enormous scale, with great implications for ecosystems. Given that take-off is the point where it all starts, whether and how the external light and internal circadian rhythm are involved in regulating the take-off behaviour remains largely unknown. Herein, we explore this issue in a migratory pest, Cnaphalocrocis medinalis, via behavioural observations and RNAi experiments. RESULTS: The results showed that C. medinalis moths took off under conditions where the light intensity gradually weakened to 0.1 lx during the afternoon or evening, and the take-off proportions under full spectrum or blue light were significantly higher than that under red and green light. The ultraviolet-A/blue light-sensitive type 1 cryptochrome gene (Cmedcry1) was significantly higher in take-off moths than that of non-take-off moths. In contrast, the expression of the light-insensitive CRY2 (Cmedcry2) and circadian genes (Cmedtim and Cmedper) showed no significant differences. After silencing Cmedcry1, the take-off proportion significantly decreased. Thus, Cmedcry1 is involved in the decrease in light intensity induced take-off behaviour in C. medinalis. CONCLUSIONS: This study can help further explain the molecular mechanisms behind insect migration, especially light perception and signal transmission during take-off phases.


Subject(s)
Cryptochromes , Insect Proteins , Moths , Animals , Animal Migration , Circadian Rhythm , Cryptochromes/genetics , Cryptochromes/metabolism , Insect Proteins/genetics , Insect Proteins/metabolism , Light , Moths/physiology , RNA Interference
4.
ACS Appl Mater Interfaces ; 16(34): 45678-45686, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39147724

ABSTRACT

Although a dust-repellent surface is desirable for lunar exploration missions, its fabrication process is complicated and time-consuming. Herein, we report a simple and fast method to fabricate a lunar dust-repellent surface by texturing on an Al substrate via nanosecond laser etching. The laser-induced photothermal effect can rapidly create hierarchical papillary structures on 25 × 25 mm Al substrates (within 30 s). Both atomic force microscopy (AFM) and in situ scanning electron microscopy (SEM) reveal that such structures enable a reduced contact area between the Al substrate and lunar dust and thus reduced adhesion. The reduced dust adhesion force of Al substrates facilitates improving their antidust performance. By optimizing processing parameters, the Al substrate etched with a laser scanning spacing of 80 µm exhibits a lower dust adhesion force (9.58 nN) due to the smallest contact area with dust. Accordingly, its static antilunar dust performance (dust coverage of 1.95%) is significantly improved compared to the pristine Al substrate (dust coverage of 12.98%). Besides, the accumulated dust on the laser-etched Al substrates with low surface adhesion force is easily cleaned up by flipping and gravity (the dust residual rates are less than 17%). The Al substrate with excellent antidust ability presents good potential for lunar exploration missions.

5.
Stem Cell Res ; 81: 103545, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39213692

ABSTRACT

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder caused by defects in the beta-galactosidase (GLB1) gene, which results in accumulation of GM1 gangliosides and related glycoconjugates in the lysosomes leading to lysosomal swelling, cellular damage, and organ dysfunction. We generated SDQLCHi080-A cell line from a patient with GM1 gangliosidosis carrying mutations of c.523C > T and c.574T > C > T in the GLB1 gene. The cell line exhibited typical iPSC morphology, expressed high levels of stemness markers, exhibited normal karyotype, and has the capability to differentiate into three germ layers. This cell line could provide a useful GM1 gangliosidosis model in vitro for further study.

6.
Front Pharmacol ; 15: 1425094, 2024.
Article in English | MEDLINE | ID: mdl-39114351

ABSTRACT

Background: Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression. Methods: A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools. Results: Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001]. Conclusion: Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.

7.
Article in English | MEDLINE | ID: mdl-39088495

ABSTRACT

Federated learning (FL) has become a popular mode of learning, allowing model training without the need to share data. Unfortunately, it remains vulnerable to privacy leakage and poisoning attacks, which compromise user data security and degrade model quality. Therefore, numerous privacy-preserving frameworks have been proposed, among which mask-based framework has certain advantages in terms of efficiency and functionality. However, it is more susceptible to poisoning attacks from malicious users, and current works lack practical means to detect such attacks within this framework. To overcome this challenge, we present DefendFL, an efficient, privacy-preserving, and poisoning-detectable mask-based FL scheme. We first leverage collinearity mask to protect users' gradient privacy. Then, cosine similarity is utilized to detect masked gradients to identify poisonous gradients. Meanwhile, a verification mechanism is designed to detect the mask, ensuring the mask's validity in aggregation and preventing poisoning attacks by intentionally changing the mask. Finally, we resist poisoning attacks by removing malicious gradients or lowering their weights in aggregation. Through security analysis and experimental evaluation, DefendFL can effectively detect and mitigate poisoning attacks while outperforming existing privacy-preserving detection works in efficiency.

8.
BMC Infect Dis ; 24(1): 804, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123121

ABSTRACT

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.


Subject(s)
Cervix Uteri , Coinfection , Papillomaviridae , Papillomavirus Infections , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Young Adult , Cervix Uteri/virology , Cervix Uteri/pathology , China/epidemiology , Coinfection/epidemiology , Coinfection/pathology , Coinfection/virology , Cross-Sectional Studies , Genotype , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/classification , Papillomavirus Infections/epidemiology , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Uterine Cervical Dysplasia/virology , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/pathology , Vaginal Smears
9.
Acta Psychol (Amst) ; 248: 104413, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39025029

ABSTRACT

In response to the public's puzzle about why maternity leave has unexpectedly failed to improve fertility problem in the Chinese context of a widespread extension of maternity leave, our study concentrates on a prevailing stigmatization phenomenon of maternity leave in the workplace, proposes the construct "maternity-leave stigma", operationalizes it, and examines its probable detrimental effect on working individuals' fertility intentions drawing on conservation of resources theory, self-verification theory, and research on stigma and psychological contract violation. Conceptually, maternity-leave stigma is a kind of workplace stigma that primarily depicts the extent to which working individuals in the reproductive period view maternity leave or the event of taking maternity leave in a biased way. It mainly consists of four subdimensions called cognitive stigma, emotional stigma, moral stigma, and consequence stigma. Based on multiple analyses of the three-stage questionnaire survey data from working individuals of childbearing age in China, Study 1 (N1 = 296, N2 = 340) acquires a 12-item maternity-leave stigma scale with good reliability and validity and Study 2 (N2 = 340) substantiates that, working individuals' maternity-leave stigma tends to directly and indirectly inhibit their fertility intentions and their anticipatory psychological contract violation from organization is the crucial mediator. Moreover, working women are inclined to display a much stronger inhibiting effect of maternity-leave stigma on fertility intentions compared to working men. Our findings therefore resolve the public's puzzle, enrich workplace stigma, deepen the implementation effectiveness research of maternity leave policy, and are of practical implications for building a fertility-friendly society.


Subject(s)
Intention , Social Stigma , Humans , Female , China , Adult , Male , Fertility , Young Adult , Women, Working/psychology , Surveys and Questionnaires , Workplace/psychology
10.
Theor Appl Genet ; 137(8): 183, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39002016

ABSTRACT

KEY MESSAGE: The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.


Subject(s)
Cercospora , Chromosome Mapping , Disease Resistance , Plant Diseases , Quantitative Trait Loci , Zea mays , Zea mays/genetics , Zea mays/microbiology , Disease Resistance/genetics , Plant Diseases/genetics , Plant Diseases/microbiology , Cercospora/genetics , Plant Breeding , Phenotype , Haploidy , Genotype , Genes, Plant
11.
Stem Cell Res ; 80: 103505, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39053320

ABSTRACT

Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a 2-year-old boy with Johanson-Blizzard syndrome carrying a compound heterozygous mutation of c.3167C>G (p.S1056X) and c.1911 + 14C>G(splicing) in the UBR1 gene. This iPSC line was free of exogenous gene, expressed stemness markers, exhibited differentiation potential, had normal karyotype and harbored the same mutations found in the patient. The iPSC cellline can serve as a disease model in drug development and novel personalized therapies.


Subject(s)
Anus, Imperforate , Ectodermal Dysplasia , Growth Disorders , Hearing Loss, Sensorineural , Induced Pluripotent Stem Cells , Mutation , Ubiquitin-Protein Ligases , Humans , Induced Pluripotent Stem Cells/metabolism , Male , Ubiquitin-Protein Ligases/genetics , Growth Disorders/genetics , Growth Disorders/pathology , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/pathology , Child, Preschool , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/pathology , Anus, Imperforate/genetics , Anus, Imperforate/pathology , Heterozygote , Nose/pathology , Nose/abnormalities , Cell Line , Exocrine Pancreatic Insufficiency/genetics , Exocrine Pancreatic Insufficiency/pathology , Deafness/genetics , Deafness/pathology , Cell Differentiation , Intellectual Disability/genetics , Intellectual Disability/pathology , Hypothyroidism , Pancreatic Diseases
12.
Bone Res ; 12(1): 41, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39019845

ABSTRACT

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.


Subject(s)
Cellular Senescence , Chondrocytes , Mice, Knockout , Mitochondria , Osteoarthritis , Animals , Humans , Male , Mice , Cartilage, Articular/pathology , Cartilage, Articular/metabolism , Cellular Senescence/drug effects , Chondrocytes/metabolism , Chondrocytes/pathology , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondria/pathology , Osteoarthritis/pathology , Osteoarthritis/metabolism , Osteoarthritis/genetics , Reactive Oxygen Species/metabolism , Stress, Mechanical
13.
Front Chem ; 12: 1435627, 2024.
Article in English | MEDLINE | ID: mdl-39021390

ABSTRACT

The lymphatic system, alongside blood circulation, is crucial for maintaining bodily equilibrium and immune surveillance. Despite its importance, lymphatic imaging techniques lag behind those for blood circulation. Fluorescence imaging, particularly in the near-infrared-II (NIR-II) region, offers promising capabilities with centimeter-scale tissue penetration and micron-scale spatial resolution, sparking interest in visualizing the lymphatic system. Although indocyanine green (ICG) has been approved by the Food and Drug Administration (FDA) for use as a near-infrared-I (NIR-I) region fluorescent dye, its limitations include shallow penetration depth and low signal-to-noise ratio. Research suggests that ICG's fluorescence emission tail in the second near-infrared window holds potential for high-quality NIR-II imaging. However, challenges like short circulation half-life and concentration-dependent aggregation hinder its wider application. Here we developed HA@ICG nanoparticles (NPs), a superior ICG-based NIR-II fluorescent probe with excellent biocompatibility, prolonging in vivo imaging, and enhancing photostability compared to ICG alone. Leveraging LYVE-1, a prominent lymphatic endothelial cell receptor that binds specifically to hyaluronic acid (HA), our nanoprobes exhibit exceptional performance in targeting lymphatic system imaging. Moreover, our findings demonstrate the capability of HA@ICG NPs for capillary imaging, offering a means to assess local microcirculatory blood supply. These compelling results underscore the promising potential of HA@ICG NPs for achieving high-resolution bioimaging of nanomedicines in the NIR-II window.

14.
Medicine (Baltimore) ; 103(28): e38908, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996139

ABSTRACT

The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathways regulated by autophagy in the RPE, thereby protecting the cells from oxidative stress and slowing RPE degeneration. In this review, we attempt to broaden the understanding of the pathogenesis of RPE dysfunction by focusing on the role and mechanism of AMPK regulation of autophagy in the RPE. The correlation between RPE cellular homeostasis and role of AMPK was determined by analyzing the structure and mechanism of AMPK and its signaling pathway in autophagy. The protective effect of AMPK-regulated autophagy on the RPE for gaining insights into the regulatory pathways of RPE dysfunction has been discussed.


Subject(s)
AMP-Activated Protein Kinases , Autophagy , Homeostasis , Retinal Pigment Epithelium , Signal Transduction , Autophagy/physiology , Retinal Pigment Epithelium/metabolism , Humans , Homeostasis/physiology , AMP-Activated Protein Kinases/metabolism , Signal Transduction/physiology , Oxidative Stress/physiology
15.
Int Immunopharmacol ; 138: 112651, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38986303

ABSTRACT

Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall, this study sheds light on the role and mechanism of PBMC in regulating macrophages. Moreover, it was found that monocytes within co-cultured PBMC differentiated into M2 macrophages in the presence of macrophages. This finding provides experimental evidence for the use of PBMC in treating inflammatory diseases, especially macrophage-depleting inflammatory diseases such as osteoarthritis.


Subject(s)
Coculture Techniques , Leukocytes, Mononuclear , Macrophages , STAT1 Transcription Factor , STAT6 Transcription Factor , Signal Transduction , Animals , Mice , Cytokines/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Macrophage Activation , Macrophages/immunology , Macrophages/metabolism , RAW 264.7 Cells , STAT1 Transcription Factor/metabolism , STAT6 Transcription Factor/metabolism
16.
Front Neurorobot ; 18: 1424158, 2024.
Article in English | MEDLINE | ID: mdl-39026563

ABSTRACT

Introduction: The secure operation of electric power transmission lines is essential for the economy and society. However, external factors such as plastic film and kites can cause damage to the lines, potentially leading to power outages. Traditional detection methods are inefficient, and the accuracy of automated systems is limited in complex background environments. Methods: This paper introduces a Weighted Spatial Attention (WSA) network model to address the low accuracy in identifying extraneous materials within electrical transmission infrastructure due to background texture occlusion. Initially, in the model preprocessing stage, color space conversion, image enhancement, and improved Large Selective Kernel Network (LSKNet) technology are utilized to enhance the model's proficiency in detecting foreign objects in intricate surroundings. Subsequently, in the feature extraction stage, the model adopts the dynamic sparse BiLevel Spatial Attention Module (BSAM) structure proposed in this paper to accurately capture and identify the characteristic information of foreign objects in power lines. In the feature pyramid stage, by replacing the feature pyramid network structure and allocating reasonable weights to the Bidirectional Feature Pyramid Network (BiFPN), the feature fusion results are optimized, ensuring that the semantic information of foreign objects in the power line output by the network is effectively identified and processed. Results: The experimental outcomes reveal that the test recognition accuracy of the proposed WSA model on the PL (power line) dataset has improved by three percentage points compared to that of the YOLOv8 model, reaching 97.6%. This enhancement demonstrates the WSA model's superior capability in detecting foreign objects on power lines, even in complex environmental backgrounds. Discussion: The integration of advanced image preprocessing techniques, the dynamic sparse BSAM structure, and the BiFPN has proven effective in improving detection accuracy and has the potential to transform the approach to monitoring and maintaining power transmission infrastructure.

17.
Heliyon ; 10(13): e33457, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39027567

ABSTRACT

Background: Dual occurrence of distinct genetic diseases is exceptionally rare, complicating both diagnosis and management when the conditions share overlapping symptoms. Case presentation: We describe a preschooler girl diagnosed with Down syndrome at 27 months who developed unexplained motor regression with age. Extensive investigations were carried out to elucidate the etiology, encompassing comprehensive neuromuscular and skeletal assessments, radiographic evaluations of the joints, electrophysiological studies, cerebral-spinal magnetic resonance imaging (MRI), hematological biochemical assays, plasma ammonia and lactate levels, full blood count analyses, echocardiography, and chromatography-mass spectrometry-based testing of amino acids, fatty acids, and organic acid metabolites in both blood and urine. Notably, significantly elevated levels of homocysteine and propionylcarnitine were detected in her blood, while urinary methylmalonic acid was also found to be abnormally high. Trio-whole exome sequencing confirmed the diagnosis as Combined methylmalonic acidemia and homocystinuria (Combined MMA and HCU), specifically due to a cblC defect, resulting from two compound heterozygous pathogenic mutations (c.217C > T and c.482G > A) in the MMACHC gene. Upon a two-month course of treatment with hydroxocobalamin and l-carnitine, the patient demonstrated moderate improvement in her motor abilities. Conclusion: Our study highlights the special and intriguing aspects of managing Combined MMA and HCU, emphasizing the value of a comprehensive diagnostic approach that integrates clinical acumen, metabolic screening, and sophisticated molecular analyses for achieving precise diagnoses in such intricate cases.

18.
Genomics ; 116(5): 110901, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39047876

ABSTRACT

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

20.
Physiol Mol Biol Plants ; 30(6): 867-876, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38974359

ABSTRACT

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

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